It is proposed to undertake an extensive investigation of metal-protein and metal-oligopeptide interactions with the intention of elucidating the structure and function of metalloprotein active sites. Examined in detail will be iron, zinc, and, particularly, copper proteins which are vital to human metabolism. This proposal is based on our recent results from powerful light scattering experiments with "blue" copper proteins and subsequent formulation of an active site model for these enzymes. Continued research in this area to explore the functional role of metal-one sulfur bonding that is fundamental to these versatile metalloproteins is crucial. A thorough investigation will require synthesis of cysteinyl peptide-metal complexes and the study of sulfhydryl protein (papain and metallothionein)-metal derivatives. This strategy will be extended to study prosthetic group-protein interaction in bicarbonate (transferrin, carbonic anhydrase), zinc (superoxide dismutase, carboxypeptidase), and flavin-containing proteins. Chemical modifications--metal ion replacement, chromophoric substrate labels, and amino acid residue derivatives--will be performed to gain a complete picture of enzyme-substrate (inhibitor) complexes from light absorption and scattering experiments. When specific reactions occur, the products will be identified structurally and by the kinetics of their formation.